Key Laboratory of Animal Physiology &Biochemistry, Nanjing Agricultural University, Nanjing 210095, P. R. China.
Jiangsu Collaborative Innovation Centre of Meat Production and Processing, Quality and Safety Control, Nanjing 210095, P. R. China.
Sci Rep. 2017 Jan 6;7:40251. doi: 10.1038/srep40251.
Betaine alleviates high-fat diet-induced fatty liver and prenatal betaine programs offspring hepatic lipid metabolism. Excessive corticosterone (CORT) exposure causes fatty liver in chickens, yet it remains unknown whether and how prenatal betaine modulates the susceptibility of CORT-induced fatty liver later in life. In this study, fertilized eggs were injected with saline or betaine before incubation, and the hatchlings were raised at 8 weeks of age followed by 7 days of subcutaneous CORT injection. CORT-induced fatty liver was less severe in betaine-treated chickens, with significantly reduced oil-red staining and hepatic triglyceride content (P < 0.05). The protective effect of prenatal betaine was associated with significantly up-regulated expression of PPARα and CPT1α, as well as mitochondrial DNA (mtDNA)-encoded genes (P < 0.05). Moreover, betaine rescued CORT-induced alterations in methionine cycle genes, which coincided with modifications of CpG methylation on CPT1α gene promoter and mtDNA D-loop regions. Furthermore, the elevation of hepatic GR protein content after CORT treatment was significantly reduced (P < 0.05), while the reduction of GR binding to the control region of affected genes was significantly increased (P < 0.05), in betaine-treated chickens. These results indicate that in ovo betaine injection protects the juvenile chickens from CORT-induced fatty liver.
甜菜碱可减轻高脂饮食诱导的脂肪肝，并可调节产前甜菜碱对后代肝脏脂质代谢的编程作用。过量的皮质酮（CORT）暴露会导致鸡脂肪肝，但目前尚不清楚产前甜菜碱是否以及如何调节 CORT 诱导的脂肪肝在生命后期的易感性。在这项研究中，在孵化前用生理盐水或甜菜碱对受精蛋进行注射，然后在 8 周龄时将孵化出的小鸡饲养，再进行 7 天的皮下 CORT 注射。与对照组相比，甜菜碱处理组的鸡脂肪肝程度较轻，油红染色和肝甘油三酯含量明显降低（P<0.05）。产前甜菜碱的保护作用与 PPARα和 CPT1α的表达显著上调以及线粒体 DNA（mtDNA）编码基因有关（P<0.05）。此外，甜菜碱还可以挽救 CORT 诱导的蛋氨酸循环基因的改变，这与 CPT1α基因启动子和 mtDNA D-环区域的 CpG 甲基化修饰相吻合。此外，CORT 处理后，肝脏中 GR 蛋白含量的升高显著降低（P<0.05），而受影响基因的控制区域与 GR 结合的减少显著增加（P<0.05），在甜菜碱处理组的鸡中。这些结果表明，鸡胚注射甜菜碱可保护幼鸡免受 CORT 诱导的脂肪肝的影响。
